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Fc-engineered antibody therapeutics with improved anti-SARS-CoV-2 efficacy

机译：FC工程抗体治疗剂，具有改善的抗SARS-COV-2功效

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摘要

Monoclonal antibodies with neutralizing activity against SARS-CoV-2 have demonstrated clinical benefits in cases of mild-to-moderate SARS-CoV-2 infection, substantially reducing the risk for hospitalization and severe disease(1-4). Treatment generally requires the administration of high doses of these monoclonal antibodies and has limited efficacy in preventing disease complications or mortality among hospitalized patients with COVID-19(5). Here we report the development and evaluation of anti-SARS-CoV-2 monoclonal antibodies with optimized Fc domains that show superior potency for prevention or treatment of COVID-19. Using several animal disease models of COVID-19(6,7), we demonstrate that selective engagement of activating Fc. receptors results in improved efficacy in both preventing and treating disease-induced weight loss and mortality, significantly reducing the dose required to confer full protection against SARS-CoV-2 challenge and for treatment of pre-infected animals. Our results highlight the importance of Fc. receptor pathways in driving antibody-mediated antiviral immunity and exclude the possibility of pathogenic or disease-enhancing effects of Fc. receptor engagement of anti-SARS-CoV-2 antibodies upon infection. These findings have important implications for the development of Fc-engineered monoclonal antibodies with optimal Fc-effector function and improved clinical efficacy against COVID-19 disease.
机译：对SARS-COV-2的中和活性的单克隆抗体在轻度至中等的SARS-COV-2感染情况下表现出临床益处，显着降低了住院治疗和严重疾病的风险（1-4）。治疗一般要求施用高剂量的这些单克隆抗体，并且在预防住院治疗患者的Covid-19（5）患者中的疾病并发症或死亡率有限。在这里，我们报告了抗SARS-COV-2单克隆抗体的开发和评估，优化的FC结构域，其显示出卓越的预防或治疗Covid-19。使用Covid-19（6,7）的几种动物疾病模型，我们证明了激活Fc的选择性接合。受体导致预防和治疗疾病诱导的体重减轻和死亡率的疗效改善，显着降低了赋予SARS-COV-2攻击的攻击和治疗预热动物所需的剂量。我们的结果突出了FC的重要性。促进抗体介导的抗病毒免疫的受体途径，不排除致病或疾病增强的Fc的可能性。抗SARS-COV-2抗体对感染的受体接合。这些发现对具有最佳Fc-效应函数的FC工程单克隆抗体的发展具有重要意义，并改善了对Covid-19疾病的临床疗效。

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  • 来源
    《Nature》 |2021年第7885期|465-470|共6页
  • 作者

    Yamin Rachel; Jones Andrew T.; Hoffmann Hans-Heinrich; Schafer Alexandra; Kao Kevin S.; Francis Rebecca L.; Sheahan Timothy P.; Baric Ralph S.; Rice Charles M.; Ravetch Jeffrey V.; Bournazos Stylianos;

  • 作者单位

    Rockefeller Univ Lab Mol Genet & Immunol 1230 York Ave New York NY 10021 USA;

    Rockefeller Univ Lab Mol Genet & Immunol 1230 York Ave New York NY 10021 USA;

    Rockefeller Univ Lab Virol & Infect Dis New York NY 10021 USA;

    Univ N Carolina Dept Epidemiol Chapel Hill NC USA;

    Rockefeller Univ Lab Mol Genet & Immunol 1230 York Ave New York NY 10021 USA;

    Rockefeller Univ Lab Mol Genet & Immunol 1230 York Ave New York NY 10021 USA;

    Univ N Carolina Dept Epidemiol Chapel Hill NC USA;

    Univ N Carolina Dept Epidemiol Chapel Hill NC USA|Univ N Carolina Dept Microbiol & Immunol Chapel Hill NC USA;

    Rockefeller Univ Lab Virol & Infect Dis New York NY 10021 USA;

    Rockefeller Univ Lab Mol Genet & Immunol 1230 York Ave New York NY 10021 USA;

    Rockefeller Univ Lab Mol Genet & Immunol 1230 York Ave New York NY 10021 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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